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印度眼镜蛇参考基因组和转录组可实现毒液毒素的全面鉴定。

The Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins.

机构信息

Molecular Biology Department, Genentech, Inc., South San Francisco, CA, USA.

MedGenome Inc., Foster City, CA, USA.

出版信息

Nat Genet. 2020 Jan;52(1):106-117. doi: 10.1038/s41588-019-0559-8. Epub 2020 Jan 6.

Abstract

Snakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually. High-quality, genome-enabled comprehensive characterization of toxin genes will facilitate development of effective humanized recombinant antivenom. We report a de novo near-chromosomal genome assembly of Naja naja, the Indian cobra, a highly venomous, medically important snake. Our assembly has a scaffold N50 of 223.35 Mb, with 19 scaffolds containing 95% of the genome. Of the 23,248 predicted protein-coding genes, 12,346 venom-gland-expressed genes constitute the 'venom-ome' and this included 139 genes from 33 toxin families. Among the 139 toxin genes were 19 'venom-ome-specific toxins' (VSTs) that showed venom-gland-specific expression, and these probably encode the minimal core venom effector proteins. Synthetic venom reconstituted through recombinant VST expression will aid in the rapid development of safe and effective synthetic antivenom. Additionally, our genome could serve as a reference for snake genomes, support evolutionary studies and enable venom-driven drug discovery.

摘要

蛇伤中毒是一种严重且被忽视的热带病,每年导致约 10 万人死亡。高质量、基因组赋能的毒素基因综合特征描述将有助于开发有效的人源化重组抗蛇毒血清。我们报告了印度眼镜蛇 Naja naja 的从头近染色体基因组组装,这是一种高度有毒且具有重要医学意义的蛇。我们的组装具有 223.35 Mb 的支架 N50,有 19 个支架包含基因组的 95%。在 23248 个预测的蛋白编码基因中,12346 个毒液腺表达基因构成了“毒液组”,其中包括 33 个毒素家族的 139 个基因。在 139 个毒素基因中,有 19 个“毒液组特异性毒素”(VST)具有毒液腺特异性表达,这些基因可能编码最小的核心毒液效应蛋白。通过重组 VST 表达重建的合成毒液将有助于快速开发安全有效的合成抗蛇毒血清。此外,我们的基因组可以作为蛇基因组的参考,支持进化研究并实现毒液驱动的药物发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b05/8075977/278af8234416/41588_2019_559_Fig1_HTML.jpg

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